It is proposed to study the etiology, pathophysiology, natural history and treatment of acute hematogenous osteomyelitis and other factors which may influence the direction and duration of this disease. To achieve this we have developed a standard experimental rabbit osteomyelitic model, reported in our preliminary results, which we hope to refine and further standardize. The model relies on systemically administered bacteria which will create a subclinical bacteremia. One limb is traumatized by minimally slipping the epiphyseal plate of the tibia on a specially constructed press which does not create instability, bone damage or hemorrhage to the plate. As the bacteria appear to be localized below the area of traumatization in the metaphysis, a typical clinical osteomyelitic condition occurs and prevails. With this model we are able to control the severity of the disease, predicting and locating lesions. Using this model the pathophysiology may be studied at daily intervals enabling a better understanding of the natural history of the disease. Once understanding the progression of the disease other influencing factors, such as trauma, immunosuppressants and dietary deficiencies may be applied and the effects carefully monitored. Having perfected the model, standard forms of treatment may be applied to the model and their effects studied. This will give the surgeon greater ability in treating the disease. It is known that early administration of antibiotics is effective in treatment, but later administration is not. These studies will answer the questions of whether antibiotics are useful after a certain length of time following the onset of the disease. It will also indicate a point in time when surgery must be used, and will predict its success. The information yielded from this project will enhance our understanding of the disease in humans. This will enable the orthopaedic surgeon to treat the disease scientifically instead of with the empirical methods which are presently used.